The mechanism of postinhibitory rebound increase in GH secretion was studied in 5 normal and 7 acromegalic subjects. Both normal and acromegalic subjects showed prompt GH decreases during the infusion of somatostatin (500 micrograms/75 min) (% decrease: 69.1 +/- 10.4 vs. 73.9 +/- 6.5) and rebound rises after its termination. The rebound rises occurred more promptly and markedly in normal controls than in acromegalic subjects, i.e. the rebound peak appeared at 15 min in normal controls and at 45 min in acromegalic patients after the cessation of somatostatin infusion. Dopamine (DA) infusion (5 micrograms/kg/min for 90 min) also induced similar inhibition and postinhibitory rebound rises in GH secretion in 6 patients with acromegaly. Although the maximum inhibitions (67.1 +/- 7.3% vs. 73.7 +/- 7.1%) and the inhibitory areas (4354.5 +/- 471.0% . min vs. 3796.5 +/- 322.5% . min) during the DA and somatostatin infusions were not different, the rebound at 15 min was significantly greater after DA than after somatostatin (p less than 0.05). All seven patients with acromegaly were TRH responsive in their plasma GH (% of basal: 93.5 to 944.3). When TRH was injected at the termination of somatostatin infusion, the rebound increase was significantly enhanced and the rebound peak appeared 30 min earlier than after single somatostatin administration. These results indicate that the mechanisms participating in the postinhibitory rebound rise are different in normal controls and acromegalic patients, and that the magnitude of the rebound differs with agents employed. Also, it is evident that the rebound phenomenon in acromegaly is possibly modified by exogenous hypothalamic releasing factors.